1. Field of the Invention
This invention relates to fertilization procedures for human females, and more particularly to an apparatus and procedure for performing such procedures.
2. Prior Art
Once every 28 days or so, in the reproductive cycle of a post-pubescent human female, a single secondary oocyte (ovum) emerges from a weakened portion of the ovary wall to which it was attached, and is carried by ciliary action along the uterine tube toward the uterus, for fertilization.
This reproductive cycle for a human female is divided into the follicular phase, which is the first 14 days, and the luteal phase, which is the last 14 days of this 28 day cycle. During the follicular phase, pituitary hormones stimulate the development of one or two small cysts in the ovary, each containing an ovum. Cells surrounding the developing ovum produce estrogen that, in turn, stimulates the growth of the endometrium, the velvet-like interior lining of the uterus. On day 13, a second hormone is released from the pituitary, causing ovulation--the release of the ovum from the ovary. The distal fingers of the fallopian tube embrace the ovum and envelope it in the distal tube (the ampulla). Fertilization, the union of the ovum and the sperm, can occur only in the ampulla. After fertilization, the zygote, (the fertilized ovum), slowly migrates down the fallopian tube, and, on the sixth day post-conception, attaches to the endometrium in the uterus (implantation). Of all of the normal reproductive activities, implantation is the most poorly understood.
The luteal phase is from day 14 to day 28. After ovulation, the ovary changes functions and produces progesterone at the exact site of ovulation. The site in the ovary is yellow, and is therefore named corpus luteum, or yellow body. The action of the progesterone on the endometrium is to stop the estrogen-mediated growth of the endometrium and prepare it for the reception and support of the developing embryo. When implantation of the embryo into the endometrium occurs, the embryo divides into two distinct cell lines; the placental line and the fetal line. The placental tissue produces human chorionic gonadotrophin (HCG), which acts to continue the ovarian corpus luteum production of progesterone for twelve weeks. After twelve weeks, the placenta produces an adequate amount of progesterone to support and continue the pregnancy. The measurement of the HCG is the pregnancy test. In normal pregnancies, HCG can be detected about day 26, and doubles every two days.
The cervix is the junction of the vagina and the intrauterine cavity. It is a three centimeter canal, lined by mucous-producing cells under direct hormonal control of estrogen and progesterone. On day 13 of the cycle, the high estrogen titre causes the cervical mucous to be thin and watery and easily traversed by sperm. For the rest of the entire 28 day cycle, the cervical mucous is thick and acts as a plug and a natural barrier which prevents entrance of sperm and oxygen into the intrauterine environment.
A transvaginal ultrasound is very helpful in the monitoring of pregnancy in early stages. At five weeks from the last menstrual period (LMP), a gestational ring is easily visualized; this is placenta on the outside and ammonitic fluid inside. At six weeks from the LMP, this gestational ring is twice the size that it was at five weeks. At seven weeks from the LMP, a heartbeat is detectable with the ultrasound. Patients are reassured that there is a 99% chance of delivery once the heartbeat is seen. The heartbeat signifies a normal 46 chromosomal embryo. The lack of a heartbeat by eight weeks from the LMP denotes a miscarriage because of imperfect chromosomes of 45 or 47.
If implantation does not occur six days after fertilization, the genetics are completely abnormal and the fertilized egg did not even divide. Therefore, the HCG pregnancy test is negative, and the patient has a normally timed menstrual flow (days 25 and 28 respectively).
Fertilization is also a function of maternal age. By age fifteen, one pregnancy may occur for two cycles (two fertilizations);--at age twenty, one fertilization for three cycles (three fertilizations);--at age thirty, one pregnancy for four to five cycles (four or five fertilizations).
This principal is also reflected in the frequency of miscarriage and of Down's Syndrome (47 chromosomes), the risk of which doubles every five years from age fifteen to age forty:
______________________________________ (age) 20 1/2000 30 1/1000 35 1/356 40 1/96 45 1/20 ______________________________________
The relationship between maternal age and both miscarriage and Down's Syndrome is due to the genetic damage in the ova caused by gamma radiation. The cumulative dosage effect of gamma radiation causes the ova to have 22 or 24 chromosomes, rather than the normal 23.
In Vitro ("in a test tube") Fertilization (IVF) offers women who face these above-identified problems, and who have a difficulty conceiving, a means of having a successful pregnancy.
In vitro fertilization is a process of removing a mature ovum from the stimulated ovary, combining the ovum with sperm outside of the body, allowing the fertilized ovum to grow and divide, and then replacing the ovum transcervically into the uterine cavity with hopes of implantation and the establishment of a pregnancy. The primary indications of IVF are tubal disease, oligospermia, endometriosis, and unexplained infertility. The specific steps in IVF and the associated success of each step are; 1. downregulation-use of a hormone to prevent the pituitary from normal stimulatory function--100%; 2. follicular development-daily injections of FSH (follicle stimulating hormone)--100%; 3. ovum retrieval-ultrasound-guided transvaginal placement of a long needle beneath the cervix in the vagina, into the peritoneal cavity, and the sequential draining of each follicle to isolate its ovum--95%; 4. actual fertilization--combining of the ovum and processed sperm--90%; and 5. embryo transfer--after fertilization has occurred, the zygotes are allowed to grow and divide for 24, 48, or 72 hours. The embryos then are withdrawn into a thin plastic tube, and the tube is used to penetrate the endocervical canal, and the embryos are injected into the intrauterine cavity. These embryos are free floating and must attach the endometrium and implant in order for the procedure to result in a pregnancy. Usually four or five embryos are transferred into the intrauterine cavity; however, even under optimal conditions, the success rate is 33% at best. The low success rate of this IVF approach is directly related to embryo transfer and poor implantation rate. The possible causes for the poor implantation rate are: 1. free floating embryos and the lack of a sustained juxtaposition of the embryo against the endometrium; 2. high O.sub.2 tension because of the transcervical embryo transfer and introduction of room air (21% O.sub.2) into a normally CO.sub.2 environment; 3. antibody/antigen interactions--the initial implantation has been postulated as a positive/negative electrical attraction-interaction between the embryo and the endometrium. A continuing juxtaposition of the embryo and the endometrium might allow implantation and factor out electrical interactions.
This type of IVF procedure can have many complications. Because of the low implantation rate per embryo, usually four or five embryos are transferred into the intrauterine cavity in hopes that one will implant. In 30% of the successful IVF cycles, twins will be produced; in 10% of IVF cycles, four to five embryos will implant. If the implantation rate could be improved, fewer embryos would have to be transferred, and the percentage of multiple births could be reduced or even eliminated.
During this embryo transfer of this procedure, pressure is applied to a syringe to expel the embryos from the tip of the transfer catheter into the intrauterine cavity. This pressure is subject to variation, and at times may push the embryos into the proximal fallopian tubes. A tubal or ectopic pregnancy will not continue as a normal pregnancy, and usually requires a surgical removal of the ectopic pregnancy. The ectopic rate for IVF is reported as two to five percent.
It is an object of the present invention to overcome the disadvantages of the prior art.
It is a further object of the present invention, to provide an apparatus and procedure which will permit a direct vision embryo transfer utilizing an intrauterine retention balloon for IVF.